Chapter 1 - Cancer Treatment during Pregnancy
Chemotherapy during Pregnancy
The administration of chemotherapy during the first trimester is associated with a considerably higher rate of spontaneous abortion and congenital malformations. Hence, chemotherapy should be avoided during this period, if at all possible. In cases in which it is urgent to start chemotherapy for maternal advanced disease during the first trimester, abortion should be considered.
Generally, exposure to chemotherapy following the first trimester does not appear to be associated with major foetal complications, particularly in the short term. However, preterm labour and pregnancy-related complications (e.g. gestational diabetes, premature rupture of membranes) appear to be higher in cancer patients treated with chemotherapy compared to those exposed only to surgery. Thus, administering standard therapy during pregnancy might not be feasible in all cases, and in some situations customised strategies could be adopted. Among such strategies, weekly fractionation of the chemotherapy dose emerges as an attractive approach. It is associated with a lower peak plasma concentration of the drug, which lowers the chances of placental crossing. In addition, it allows close monitoring of the pregnancy and easy interruption of the drug administration, if needed.
Importantly, the safety of the different chemotherapeutic agents is not equivalent when administered during pregnancy (List below). Some agents should be avoided even during the second and third trimester. This will be covered in more detail in the subsequent sections.
The pharmacokinetics of most chemotherapeutic agents is altered during pregnancy. These drugs are partly metabolised by the placenta, resulting in a reduced maximum plasma concentration (Cmax) and a higher renal clearance when administered during pregnancy. However, it is not clear whether this has any clinical implications on their efficacy during pregnancy. Using higher dosages of chemotherapy during pregnancy is not recommended, but the actual body weight should be used, without adapting for the pregnant state.
Estimated Risk of Pregnancy Complications with Systemic Anti-cancer Therapy When Administered during the Second and Third Trimester of Gestation
High risk: “prohibited”
Medium risk: “use with caution”
Low risk: “allowed”
Note: This classification is not based on the Food and Drug Administration classification, but rather on the interpretation made by the authors of the limited available preclinical and clinical data.
Hormonal Agents during Pregnancy
The use of tamoxifen during pregnancy has been shown to be associated with ambiguous genitalia in animals. Similar observations were also noted in sporadic case reports in humans. Thus tamoxifen should be avoided during pregnancy. Caution is advised in young breast cancer patients who are on tamoxifen as a part of their adjuvant therapy. These patients should be asked to use contraception during treatment. If pregnancy has occurred, patients should be informed that there is a potential risk of foetal malformations secondary to tamoxifen in order to make an informed decision on whether they would like to proceed with the pregnancy.
Monoclonal Antibodies during Pregnancy
Monoclonal antibodies are large molecules that require active transport to cross the placenta and reach the foetus. Such mechanism is activated only following the first trimester. Hence, unlike chemotherapy and hormonal agents, early exposure to monoclonal antibodies is unlikely to be associated with foetal defects. This could be relevant in patients who become accidentally pregnant during maintenance therapy (trastuzumab in breast cancer; rituximab in non-Hodgkin’s lymphoma). In these cases, the drug should be stopped once pregnancy has been established, yet abortion does not need to be considered. In pregnant cancer patients, prolonged administration of monoclonal antibodies following the first trimester could be associated with major pregnancy and foetal complications. This is rather drug-dependent and will be discussed in more detail in the subsequent sections.